In April 2015 a team of Chinese scientists reported in a little known journal, Protein & Cell, the use of CRISPR/Cas9 to cleave and then repair the HBB gene in nonviable human embryos (Liang et al. 2015). The mutated form of HBB causes B-thalassemia, a potentially fatal blood disease. To say the experiment prompted controversy is an understatement. It was published on the heels of two high-profile commentaries in Nature and Science, both of which urged caution about using CRISPR/Cas9 and other technologies to edit the human germline; the Nature authors went so far as to recommend a stop of experiments precisely like the one reported in Protein & Cell (Baltimore et al. 2015; Lanphier et al. 2015). The Liang et al. paper seemed to fly in the face of the recommendations. Though the researchers used triponuclear human embryos (an essential fact missed by some of the breathless reporting in the days after), they designed the experiment as a test of a possible therapeutic strategy. If eventually proven safe, a diseased embryo would be corrected using CRISPR/Cas9 with the intent of eventually making a healthy baby. Importantly, the authors reported notable off-target effects of CRISPR-based gene editing, low efficiency of homologous recombination directed repair (HDR), mosaicism, and unwanted mutations. They concluded:

Taken together, our data underscore the need to more comprehensively understand the mechanisms of CRISPR/Cas9-mediated genome editing in human cells, and support the notion that clinical applications of the CRISPR/Cas9 system may be premature at this stage. (364) […]